In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
Genetic abnormalities account for a wide number of pathologies, including pathologies caused by chromosomal aneuploidy (e.g., Down syndrome), germline mutations in specific genes (e.g., sickle cell anemia), and pathologies caused by somatic mutations (e.g., cancer). Diagnostic methods for determining genetic anomalies have become standard techniques for identifying specific diseases and disorders, as well as providing valuable information on disease source and treatment options.
Copy number variations (CNVs) are alterations of genomic DNA that correspond to specific regions of the genome—including entire chromosomes—that have been deleted or duplicated. CNVs can be caused by genomic rearrangements such as deletions, duplications, inversions, and translocations. CNVs have been associated with various forms of cancer (Cappuzzo F, Hirsch, et al. (2005) J Natl Cancer Inst., 97(9):643-55), neurological disorders, including autism (Sebat, J., et al. (2007) Science 316(5823):445-9), and schizophrenia (St. Clair, D., (2008). Schizophr Bull 35(1):9-12).
Therefore, there is a need for methods of screening for copy number variations that employs an efficient, reproducible assay and detection system.